The telomere and telomerase hypothesis of aging and cancer is based on the findings that most human tumors have telomerase activity while almost all normal human somatic cells do not. Telomeres are nucleoprotein structure that located 100-300 kb from the end of linear eukaryotic chromosomes (Blackburn et al, 2001; Yoo & Robinson, 2000). Human telomeres consist of thousand repetitive sequences TTAGGG with ranging from 5 to 20 kb (Figure 1) (Martin, 2002). In human cell, there are 92 telomeres which have several functions including protecting chromosome ends, to maintain chromosome stability, serve as an attachment point to the nuclear matrix and also involve in the cell replication.
The incidence of HbE/beta (HbE/β) thalassaemia is increasing in Asian countries, including Malaysia. HbE/β thalassaemia is widely acknowledged to have a diverse phenotypic spectrum despite having the same primary genetic background [1,2,3]. Thus, there are HbE/β thalassaemia patients who receive unnecessary treatments which leads to side effects [4], reduced quality of life and wasting health care resources. Ideally, the treatment and management of thalassaemia patients are individually tailored in order to minimise side effects and optimise health care costs. Genetic variants have been widely acknowledged to influence the variability of human phenotypes. Presence of unique genetic modifiers are believed to cause the diversity in HbE/β thalassaemia severity. Milder disease course has been found to be highly associated with Xmn1-Gγ polymorphism (rs7482144), a SNP at HBG2 promoter [1,5,6,7]. So far, there is no association study between Xmn1-Gγ polymorphism and HbE/beta thalassaemia disease severity in Malaysia. This study aims to optimise PCR-RFLP technique for detection of Xmn1-Gγ polymorphism, to determine the frequency of Xmn1-Gγ polymorphism in HbE/β thalassaemia patients and finding its association with the severity of HbE/β thalassaemia patients. This hospital-based cross-sectional study was performed using archived genomic DNAs from 58 subjects with their respective research pro formas. Selected datas were extracted from the pro formas in order to classify patients into 3 disease severity groups using the scoring system by Sripichai et al., (2008) based on 6 parameters. The archived genomic DNAs were genotyped employing Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. The genotypes were categorised into homozygous variant, heterozygous and homozygous wild type. The genotypes detected were then validated using DNA sequencing analysis. Appropriate statistical analysis was used to determine the association of Xmn1-Gγ polymorphism with the clinical severity of HbE/β thalassaemia. This study had successfully optimised the PCR-RFLP technique for detection of Xmn1-Gγ polymorphism. Out of 58 subjects, the Xmn1-Gγ polymorphisms were detected in 40 subjects (69%) with the majority being heterozygous (CT) (n=38, 66%) and there were only 2 (3%) homozygous variant (TT) subjects. Homozygous wild type (CC) were detected in 18 (31%) subjects. There were no significant association of Xmn1-Gγ polymorphism with the severity of HbE/β thalassaemia patients with p-value of 0.65 for genotype and 0.58 for allele, respectively. In conclusion, this study showed no significant association of Xmn1-Gγ polymorphism with milder disease severity of HbE/β thalassaemia patients. This can be a true finding for the patients in North East Malaysia or due to small sample size. Thus we recommend to have a larger study in order to validate the association of Xmn1-Gγ polymorphism with HbE/β thalassaemia severity. In addition, there may be other genetic factors that interact with Xmn1-Gγ polymorphism as it was not possible to consistently predict phenotype and severity from the presence of Xmn1-Gγ polymorphism alone.
Telomerase has become important in molecular genetics since its discovery in 1984. The study of telomere in ciliate Tetrahymena thermophilia since 4 decades ago has led to the discovery of telomerase that was discovered by Elizabeth Blackburn and her postgraduate student, Carol Widney Greider in 1984. Later in 2009, Jack William Szostak together with Greider and Blackburn were awarded the Nobel Prize in Physiology or Medicine for their discovery. (Copied from article).
Introduction: Exome sequencing technology which is part of Next Generation Sequencing (NGS) is known for detection of various disease mutations through commercially available platforms. Less reports in identifying genetic variation in non-syndromic cleft lip with or without cleft palate (NSCL/P) in Malaysia had embarked for discovery of susceptible genes to fill in the gaps with the healthcare delivery for a better treatment and management to the patients and family. Methods: Whole exome sequencing was carried out on two Malay NSCLP patients. Blood samples were withdrawn and intact DNA was extracted, fragmented, purified and hybridized using exome sequencing capture and sequenced with Agilent 2100 Bioanalyzer platform. Bioinformatic analyses were done and reviewed with GenBank and PubMed database. Variants were filtered based upon a high impact variant. Results: We have identified single nucleotide polymorphisms in 2 genes (PDE4DIP and PDE11A) and InDels frameshift mutations in 4 genes (PDE4DIP, LTBP4, MMP12 and MMP28). Our preliminary study presents the successful application of whole exome sequencing to elucidate the genetic basis of NSCLP in Malays. Conclusion: Mutations that have been identified would shed more light on the susceptible genes to non-syndromic clefts and further investigation shall be carried out to confirm.
Muscular dystrophy is a group of diseases that result in progressive muscle weakness and atrophy. Duchenne Muscular Dystrophy (DMD) is classified as dystrophinopathy and is an X-linked recessive disease. It is caused by alterations in the dystrophin gene at Xp21.2 encoding 79 exons [1]. It is characterised by progressive muscle wasting that begins at 3 to 5 years, delay in motor development and eventually wheelchair confinement followed by premature death at about 30 years from cardiac or respiratory complications [2]. Genetic etiology of cases of DMD in Malaysia are still scarcely reported. Here, we report the genetic cause in the case of an 11-year-old Kelantanese Malay boy who has progressive muscle weakness since 5 years old. He has difficulty in getting up from sitting and supine position also in climbing up stairs until 1st floor. He has a strong family history of DMD and musculoskeletal problems. His younger brother was diagnosed with DMD by molecular analysis and his maternal uncle died at the age of 16 with musculoskeletal problems but was never investigated. Physical examination revealed no dysmorphic features, positive Gower sign with absent tounge fasciculation. On neurological examination, tendon reflexes and muscle tone for limbs were normal. Muscle power for bilateral upper limbs were normal, however, bilateral lower limbs showed slight reduction in muscle power with calf hypertrophy.
Complex chromosome rearrangements (CCRs) are structural aberrations or rearrangements involving three or more cytogenetics breakpoints on two or more chromosomes [1]. Balanced and unbalanced are known to have significant risk of mental retardation and phenotypic anomalies. CCRs are also associated with infertility in males and recurrent abortion in females. Here we report one case of apparently balanced CCR involving three chromosomes 3, 5 and 12 in a child with abnormal features. G banding and FISH were performed to clarify the nature of this complex abnormality.
Introduction: Age-related macular degeneration (ARMD) is an ocular degenerative disorder that associated with impairment of central vision. Oxidative stress plays an important role in the pathogenesis of ARMD. The aim of this study was to determine the level of antioxidant enzymes (catalase and glutathione peroxidase) in tears among Malay ARMD patients. Methods: A cross sectional study was conducted between September 2015 and November 2017 among Malay ARMD patients. Schirmer paper was used to collect the tear samples. The level of catalase and glu- tathione peroxidase level in tears was evaluated using commercially available oxidative stress marker kits. Results: A total of 136 Malay ARMD patients were recruited into the study with 68 controls. Mean tear catalase and gluta- thione peroxidase levels were significantly lower in ARMD patients (1348.97 SD 109.11 µM and 453.87 SD 41.96 U/L respectively) as compared to the control group (1453.38 SD 38.87 µM and 502.28 SD 34.29 U/L respectively) (P